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Abstract:

These studies have investigated the effects of fetal treatment with dexamethasone on the fetal cardiovascular, endocrine and metabolic responses to a 1h episode of acute hypoxaemia occurring both during, and 48 h following, the period of dexamethasone treatment in fetal sheep at 0.8 of gestation. Parallels have been drawn with the normal maturation of the cardiovascular, endocrine and metabolic responses to acute hypoxaemia by investigating developmental changes in the patterns of these responses close to term, and correlating them with the preparturient increase in fetal plasma glucocorticoid concentration. Mechanisms mediating the changes in the cardiovascular responses to acute hypoxaemia in the dexamethasone-treated and late gestation fetuses have been addressed by measuring the associated changes in fetal plasma concentrations of vasoconstrictor hormones (noradrenaline, adrenaline, arginine vasopressin, angiotensin II and neuropeptide Y), hormones associated with the hypothalamo-pituitary-adrenal axis (ACTH and cortisol), by assessing changes in the pressor and vasopressor responses to exogenous bolus doses of phenylephrine, arginine vasopressin and angiotensin II, and the chronotropic responses to exogenous isoprenaline, and by constructing chemoreflex and baroreflex function curves. Finally, to examine the possible role of changes in myocardial responsiveness to muscarinic cholinergic and β-adenergic stimulation in mediating alterations in the fetal heart rate response to acute hypoxaemia with glucocorticoid treatment or advancing gestational age, a novel Langendorff, biventricular, isolated, perfused fetal sheep heart preparation was developed.